This invention is related to the fields of chemistry and nuclear chemistry. This invention is the result of a contract with the Department of Energy (Contract No. W-7405-ENG-36) .
Positron emission tomography (PET) is used to generate images of the human body which aid in medical treatment and research. The images provide structural information in high resolution and, due to biochemical activity of a radiopharmaceutical used in the imaging, the images also provide information regarding function of organs and tissues. To make a PET image, the patient is intravenously infused with a PET agent, which is a radiopharmaceutical. The biochemistry of the PET agent determines how the agent distributes within the patient's body. The PET agent undergoes radioactive decay, emitting positrons. The positrons encounter electrons very near to their point of emission and are thereby annihilated. The annihilation of each positron results in the release of two 511 keV gamma photons at very close to 180 degrees from one another. The patient is encircled by an array of gamma photon detectors. Coincidence circuitry is used to detect the gamma photons and the information is stored in a computer. After the scan is complete, an image is constructed by the computer using tomographic algorithms. The PET agent is a substance comprised of a very short-lived radioisotope such as fluorine-18, carbon-11, nitrogen-13, or oxygen-15. These radioisotopes are produced using a cyclotron, which must be in the very near vicinity of the PET facility so that the agent can be used before it undergoes radioactive decay and becomes useless for the purpose. Because a cyclotron is very expensive to construct and operate, the use of PET is generally limited to major medical facilities.
The isotope of arsenic having an atomic weight of 72 has potential for use as a PET agent. It has a 26.5 hour half-life, emits a 2.5 MeV positron, and is formed by the radioactive decay of selenium having an atomic weight of 72. Arsenic-containing bone, brain, and tumor seeking substances already exist. The versatile chemistry of arsenic will permit the synthesis of many potentially valuable PET radiopharmaceuticals. Compounds such as arsenic analogs of phenothiazines will be useful for PET receptor binding studies. Such compounds will also allow the study of the modes of action and metabolism of these tranquilizers and possibly lead to a better understanding of schizophrenia. An organic arsenite has been shown to cross the blood-brain barrier, thus permitting imaging of cerebral tumors and trauma. Methods are now being developed to label monoclonal antibodies with arsenic so that tumor-specific PET imaging may be accomplished. It is believed that use of As-72 will permit early detection of lung cancer by allowing very small tumors to be shown on PET images. The potential utility of arsenic-72 is not limited to PET and other nuclear medicine applications. It is believed that there will be numerous applications in toxicology, metabolism, biochemistry, biology, and environmental science. As-72 will be useful both where arsenic compounds may be used and as a tracer for addition to other compounds. Many of these applications will require a very high specific activity of the tracer isotope.
The present invention provides a method and apparatus for generating arsenic-72 at the site of PET imaging equipment without the use of massive and expensive equipment. It provides a solution to problems of other methods which require the use of difficult to handle gases, such as hydrogen fluoride, or involve steps which are quite difficult to automate. An electrochemical technique which has been used has not produced As-72 which is sufficiently free from selenium. The generator of this invention provides the radioactive isotope As-72 at the site of use by repetitively separating As-72 from a parent substance comprised of Se-72 which can be re-used by simply allowing time for the As-72 to form after each separation. Without the present invention, As-72 would have to be transported to the point of use and used within about one day after its isolation from Se-72. The useful life of the parent substance of the present invention depends on the half-life of selenium-72, which is about 8.5 days, rather than on the half-life of As-72. It is expected that, with the methods and apparatus of the present invention, parent substance need be shipped to a location of use only about every four weeks. The generator will be used in a clinical laboratory on a routine basis and therefore must be reliable, easy to use, and safe with respect to radiation, and chemical and physical hazards. The product of the generator must be biologically sterile so that it provides a sterile and non-pyrogenic product for use within the human body, though there will be some uses as a tracer where sterility and non-pyrogenicity will not be required.